PubMed Health⌕ Search

Biomedical subjects

M Samama

Publications and source records attributed to M Samama.

At least 91 records · Page 5Linked to original sources
PubMed1988

Importance of a 3-O-sulfate group in a heparin pentasaccharide for antithrombotic activity.

Previous theoretical and experimental evidence led to the formulation of a specific pentasaccharide structure which represents the site in heparin for binding to antithrombin III. This pentasaccharide was subsequently synthesized. A pentasaccharide of the same structure but lacking only the sulfate group on the hydroxyl group of the middle glucosamine (position C-3) was also synthesized to test the structure - activity relationships. Previous biochemical studies showed the 3-O-desulfated pentasaccharide to have a low affinity binding to AT III and to be devoid of the high anti-factor Xa activity characteristic of the pentasaccharide. Our in vivo studies, in a venous stasis thrombosis model proved the 3-O-desulfated pentasaccharide, at equigravimetric dosages, to be devoid of the antithrombotic activity previously reported for the pentasaccharide. These studies confirm the fact that inhibition of factor Xa at a high level of activity produces an antithrombotic effect.

Animals↗
PubMed1988

The inhibition of the generation of thrombin and the antithrombotic effect of a pentasaccharide with sole anti-factor Xa activity.

A chemically synthesized heparin pentasaccharide (Institut Choay, Paris, France) has been shown to exhibit an antithrombotic action in a rabbit stasis induced thrombosis model, in an IV dose range of 25 to 200 micrograms/kg (0.5 to 3.5 micrograms/ml plasma circulating concentrations). Ex vivo plasma analysis from treated animals revealed expected anti-factor Xa activity but no direct inhibitory effect against thrombin. Global anticoagulant activities were not found by PT and APTT methods. Platelet activation remained unaffected at the antithrombotic dosages of pentasaccharide. To more specifically elucidate the anti-factor Xa mediated antithrombotic mechanism of action of this pentasaccharide, it was studied in several thrombin generation assays. Pentasaccharide added to human and rabbit plasmas in vitro from 0 to 5.0 micrograms/ml produced a concentration dependent effect up to a 35 to 50% inhibition of generated thrombin. In ex vivo studies similar concentration dependent inhibition of thrombin generation was observed. Analysis of plasma obtained from animals in which a complete antithrombotic effect was observed in vivo demonstrated an approximate 45 to 55% inhibition of thrombin generation. These results indicate that a relationship exists between the pentasaccharide induced inhibition of experimental venous stasis thrombosis and the inhibition of thrombin generation.

Animals↗
PubMed1988

Low molecular weight heparin compared with unfractionated heparin in prevention of postoperative thrombosis.

Three consecutive randomized open studies have been carried out to determine the optimal dosage of low molecular weight heparin (LMWH) in the prevention of postoperative thrombosis in general surgery (892 patients). All patients undergoing abdominal, gynaecological, thoracic or urological surgery were over 40 years old and presented at least one of the following risk factors for thrombosis: previous thromboembolism, obesity, varicose veins, malignancy (30 per cent), pre-operative hospitalization over 5 days, oestrogen therapy, chronic cardiac disease or bronchitis. Isotopic venous thrombosis and bleeding complications were assessed after subcutaneous administration of a LMWH fragment (LMWH, Enoxaparine) or unfractionated heparin (UH). The three studies compared 3 X 5000 units UH daily with 1 X 60 mg, 1 X 40 mg, 1 X 20 mg LMWH daily. Thromboembolic events rates were not significantly different from group to group (UH: 3.8 per cent, 2.7 per cent, 7.6 per cent respectively compared with LMWH: 2.9 per cent, 2.8 per cent, 3.8 per cent). Bleeding episodes including wound haematoma formation, perioperative blood losses and systemic haemorrhage were not significantly different in patients receiving LMWH or UH. Significant decreases in haematocrit and haemoglobin were only observed in patients receiving 60 mg Enoxaparine (as compared to UH). An analysis using the 'intention to treat' approach gave results consistent with those of an analysis of good compliers. An overview of isotopic thromboses in the three studies gave no evidence of differences amongst the effects of the three doses of LMWH (P = 0.20), and pooling the results of the three studies using the Mantel-Haenszel procedure gave no evidence of a global difference between Enoxaparine and UH (P = 0.54). These results suggest that an optimal dosage of 20 mg/day of Enoxaparine is safe and effective in the prevention of postoperative thrombosis in this population.

Aged↗
PubMed1988

Defective thrombolysis due to collagen incorporation in fibrin clots.

The migration of fibroblasts into a clot may be responsible at least in part, for its organization, thus leading to a defective thrombolysis. We have shown that collagen incorporated in a fibrin clot induces a dramatic decrease in fibrinolysis. Despite the fact that plasminogen binds to collagen, tissue plasminogen activator induced plasminogen activation in the presence of fibrin is only slightly decreased by the presence of collagen. This rather suggests that collagen induces a modification in clot structure, by rendering fibrin less accessible to fibrinolytic enzyme.

Animals↗
PubMed1988

Age-related changes in factor VII activation in healthy women.

1. To investigate the age-related changes in factor VII activation in healthy women, a regular factor VII clotting assay (factor VIIc) was carried out simultaneously with a new enzyme immunoassay for the quantification of antigen factor VII (factor VIIag). 2. Both factor VIIc and factor VIIag levels were positively correlated with age (r = 0.79 and r = 0.62, respectively, n = 25, P less than 0.001). The rise with age in factor VIIc was steeper than in factor VIIag and the ratio of factor VIIc to factor VIIag (an indicator of the activity state of factor VII) increased with age (r = 0.42, P less than 0.05). 3. The results show that an increased conversion of native single-chain factor VII to the fully active double-chain form is associated with advancing age in women. 4. This finding is consistent with a possible role of activated factor VII in the pathogenesis of thrombo-occlusive vascular disease in women.

Adult↗
PubMed1988

Comparison of thrombolytic, fibrinolytic, and fibrinogenolytic properties of tissue plasminogen activator, streptokinase, single-chain urokinase, high molecular weight and low molecular weight urokinase in human plasma in vitro.

Thrombolytic, fibrinolytic, and fibrinogenolytic properties of tissue plasminogen activator (t-PA) from melanoma cells (mt-PA), recombinant t-PA (rt-PA), streptokinase (SK), single-chain urokinase plasminogen activator (scu-PA), and high and low molecular weight urokinase (HMW UK, LMW UK) were compared in vitro by means of systems using human plasma. Thrombolytic activities were tested on standard or labeled hanging clots. When compared on the basis of urokinase international units, t-PA appeared to be slightly more active than scu-PA and streptokinase, and about 10-fold more active than both preparations of UK when they were diluted in plasma. Fibrinolytic activity was evaluated by measuring the lysis time of recalcified plasma containing variable amounts of thrombolytic agents. t-PA was shown to be twice as active as HMW UK, which was itself more active than LMW UK. When scu-PA and both types of UK were compared on bovine fibrin plates, they showed similar fibrinolytic activity, but the t-PA calibration curve was not parallel to those obtained with UK and scu-PA. Relative thrombolytic and fibrinogenolytic properties were studied for each thrombolytic agent. For similar thrombolytic activities, fibrinogenolysis provoked by scu-PA was less marked than with t-PA and with both UK, while SK showed the highest activity. Our results demonstrate that the thrombolytic/fibrinogenolytic ratio is much more favorable to t-PA and scu-PA than to both forms of UK. Another observation clearly shows that fibrinogenolysis can be induced in vitro in human plasma by high doses of t-PA. This consequence may be important since the therapeutic use of t-PA can be associated with high concentrations of t-PA, and thus t-PA infusion could lead in vivo to severe fibrinogen breakdown. In addition, the methodology described could be useful in standardizing comparison between different species of thrombolytic agents.

Fibrinogen↗
PubMed1988

Pharmacokinetics of low molecular weight heparins.

Low molecular weight heparin (LMWH) fragments have recently been proposed as antithrombotic drugs. Several fractions and fragments have been studied in human healthy volunteers: Enoxaparin (Lovenox) from Pharmuka, Fraxiparin from Choay, Fragmin from Kabi, LHN1 from Novo laboratories. The pharmacokinetics of LMWH are clearly different from those of unfractionated heparin as demonstrated by a small group of studies. In our laboratory, we undertook one study with enoxaparin. After intravenous and sub-cutaneous injection the clearance half-life of the different LMW heparins is about 3 to 4 hours. It is significantly longer for LMW heparin than for unfractionated heparin. The half-life of anti-IIa activity is similar for LMW heparins and for unfractionated heparin. However, contrary to unfractionated heparin, there is, for Enoxaparin, a difference between the two activity half-life. The anti-IIa activity half-life is smaller than that of anti-Xa activity. After intravenous and sub-cutaneous injection of 30 to 40 mg of the different fragments and fractions the biodisponibility of LMWH S.C.(A.U.C.) I.V.(A.U.C.) was about 4 times higher when compared to unfractionated heparin injected at a dose of 29 mg. In a recent study with 12 volunteers, using S.C. administration of 20, 40, 60, and 80 mg of Enoxaparin, we were able to demonstrate a good linearity between the area under the curves and the injected doses. Standard heparin is mainly cleared by a cellular mechanism while LMWH is essentially cleared by a renal mechanism. Anti-Xa activities obtained by the chromogenic technique are higher than those obtained in human plasmas with a competitive binding assay and with labelled Enoxaparin in the dog and in the rat. The persistent anti-Xa activity may be mediated by some compounds released by Enoxaparin.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1988

[Actilyse: biological aspects].

Alterations of coagulation and fibrinolysis induced by administration of single or two chains rtPA are detailed from personal and published results. One should differentiate between the thrombolytic activity, responsible for the efficacy of the drug on thrombosis and the systemic fibrinolytic activity, inducing the decrease in fibrinogen and coagulation factors which probably contribute as to the risk of bleeding, mostly related to invasive explorations (arterial punctures, catheters...), but possibly spontaneous. Few assessments are made: a sufficient plasma level of rtPA should be present to obtain a good efficacy; the degree of fibrinogen decrease is variable between individuals, although it is moderate in most patients (80% of cases); results of the measurements of fibrin degradation products are disappointing and do not allow the laboratory diagnosis of thrombus dissolution. Concerning the risk of re-occlusion, a careful monitoring of heparin treatment may reduce this risk but further studies are needed.

Fibrinolysis↗
PubMed1988

[Hemorrhagic risk in intravenously administered thrombolytic treatment in acute myocardial infarction].

163 patients aged from 27 to 70 years (mean 52 +/- 10 years), including 152 men and 11 women, received a thrombolytic treatment within the first 6 hours (mean 192 +/- 73 mn) of a myocardial infarction. 61 patients received streptokinase (SK) intravenously (group 1), 64 patients, single-chain rt-PA (group 2), 11 patients, two-chain rt-PA (group 3), 11 patients, rt-PA followed by intracoronary streptokinase (group 4), and 16 patients, acyl enzyme (group 5). In addition, all patients had heparin and 86 (53%) had aspirin. Immediately after thrombolysis, coronary arteriography was performed in 95 patients (58%), and this was followed by transluminal angioplasty in 49 of them (30%). The infarction was either anterior (n = 81) or inferior (n = 78) or lateral (n = 4). No fatal or neurological bleeding occurred. 17 haemorrhagic complications were observed; 5 of these (3%) were severe, requiring blood transfusion and, in 1 case, surgery; 12 were significant (7.4%) and produced changes in haematocrit. Nine of the 17 haemorrhages were associated with catheterization and localized to the site of arterial puncture. Severe bleeding occurred in patients treated with intravenous SK (3/61) or with rt-PA followed by intracoronary SK (2/11). There was a significant difference in the incidence of spontaneous bleeding between the SK group (4/61) and the single-chain rt-PA group (0/64; p less than 0.05). In the latter group, the minimum fibrinogen level was lower in patients who had a haemorrhagic complication.(ABSTRACT TRUNCATED AT 250 WORDS)

Acute Disease↗
PubMed1988

[Arterial thrombolysis. Review and future prospects].

After describing the mechanism of action, results and local and general complications of classical thrombolytic agents (streptokinase and urokinase) administered systemically, locally and peroperatively, then of modern thrombolytic agents (acyl enzyme, tPA and scuPA), the future perspectives of arterial fibrinolysis are discussed. These are based upon: analysis of the comparative efficacy of the different thrombolytic agents in the light of results seen, not only in peripheral arterial pathology but also in other indications, as in coronary pathology; discussion of the methods of administration of the thrombolytic agent in such a way as to obtain an optimal local concentration and at the same time reduced systemic fibrinolysis. better definition of the indications of thrombolysis in acute ischemia of the limbs in comparison with other therapeutic approaches, in particular surgery, taking into account the degree of ischemia, of etiological mechanism and the site of the arterial obstruction.

Enzyme Precursors↗
PubMed1988

[Is Behçet's disease associated with characteristic abnormalities of coagulation and fibrinolysis? Apropos of 70 case reports].

The frequency of thrombotic episodes in patients with Behçet's disease prompted us to study their hemostasis. Seventy patients were investigated and 27 of them (38%) had history of venous thrombosis; they were compared to 27 healthy subjects and to 16 hospitalized patients in whom the diagnosis of Behçet disease was ruled out. Fibrinolytic activity after a 10 minute venous occlusion was significantly decreased while fibrinogen, factor VIII and von Willebrand factor was increased as well as the tPA inhibitor (PAI-I): the last 3 proteins are synthetized by the endothelial cell. No significant difference was observed between patients with or without history of thrombosis. Coagulation and fibrinolysis changes observed are not specific of Behçet disease since they were also found in a population of patients without Behçet disease and without history of thrombosis.

Adolescent↗
PubMed1988

[The eccentriplate device on the Dideco Vivacell cell separator for the collection of platelets].

When adapted to the Dideco Vivacell cell separator, the eccentriplate system allows preparation of leukocyte-poor platelet concentrates. Results of its use on 84 procedures showed that a mean of 4.51 x 10(11) platelets were removed in less than 2 hours with a particularly low level of leukocyte contamination: 2.6 x 10(8). Study of platelet function showed them to be altered more by eccentriplate than by conventional removal with the same apparatus. Analysis of recirculation in vivo corroborated the functional anomalies observed with all aggregating agents (with the exception of arachidonate). These anomalies were associated with a quantity of platelets collected at the lower limit of French norms: 30% of the concentrates contained less than 4 x 10(11) platelets. These findings indicate the need for improvement in the eccentriplate system.

Adult↗
PubMed1988

[Acquired factor VII inhibitor: treatment using high-dose immunoglobulins, corticotherapy and plasma exchange].

A 62 year old man presented a diffuse hemorrhagic syndrome related to the presence of an acquired factor VII inhibitor (proconvertin). Autoantibodies were of the IgG class and no subjacent disease was detected during a 7-month follow up. Treatment with high-dose polyvalent immunoglobulins was ineffective, and the onset of an intracerebral hemorrhage required therapy by a series of plasma exchanges combined with immunosuppressive treatment. The plasma inhibitor was no longer present after the first exchange and clinical and biological remission was rapid.

Cerebral Hemorrhage↗